This laboratory is concerned with identifying nutritional or environmental factors inherent in Western culture which contribute to the high risk of colonic carcinoma. In this project a bacterial test system (using mutants of S. typhimurium LT2) will be applied for the detection of carcinogens/mutagens in the stool and urine of rats fed various diets with or without a procarcinogen 1,2 dimethylhydrazine (DMH). While DMH is not a common food or environmental contaminant, it shares a pathway in common with other known, or suspected, as well as presumably unknown procarcinogens, namely: 1) absorption from the gut; 2) modification or partial degradation and glucuronide formation within the liver; 3) excretion in the bile, and 4) ultimate activation in the colon by bacterial populations which possess B-glucuronidase. Various protein, fat, carbohydrate diets with or without antimicrobials will be utilized to interrupt the entro-hepatic cycle within the gut and modify the formation of the reactive intermediate methylazoxymethanol from its glucuronide. Such alterations are associated with either an increased or decreased incidence of colonic carcinomata or polyps in this model. Application of the bacterial test system for the detection of mutagens/carcinogens in these studies serves a dual role. First, it provides an opportunity to assess the applicability of such a system to detect a known carcinogen in urine and feces of animals fed a known procarcinogen. In so doing, methodology will be evolved for the extraction of a known carcinogen from the stool. This procedure will be adopted for the examination of human stools for unknown carcinogens at a future date. Second, the utilization of this test system in animals fed various types of high fat diets without a carcinogen will provide information concerning the formation of mutagens/carcinogens or possibly promoter substances directly from the diet or indirectly from host metabolites (i.e., abnormal bile salts). Detection of such agent(s) utilizing the bacterial test system will obviously lend validity to the concept. More importantly, it will provide a valuable tool for tracing the derivation of this agent(s), and provide an approach for its ultimate control or elimination from the environment.